tbuckley/cabot-search huggingface dataset:
Testosterone Recovery Following Androgen Suppression and Prostate Radiotherapy (TRANSPORT): Individual patient data meta-analysis from the MARCAP Consortium.
Authors: Wee Loon Ong, Holly Wilhalme, Jeremy Laurence Millar, Allison Steigler, James William Denham, David John Joseph, Soumyajit Roy, Shawn Malone, Nicholas George Nickols, Matthew Rettig, Luca Faustino Valle, Michael L. Steinberg, Yilun Sun, Nicholas George Zaorsky, Daniel Eidelberg Spratt, Amar Upadhyaya Kishan
Journal: Journal of Clinical Oncology (2023)

366 Background: The kinetics of testosterone recovery (TR) vary following cessation of androgen deprivation therapy (ADT) of various durations when given in combination with radiotherapy for prostate cancer. Time to TR will impact on quality of life. We aim to identify factors affecting the time to TR following ADT use. Methods: We included trials of prostate radiotherapy and ADT in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) consortium for which prospectively collected serial testosterone data is available. Time to non-hypogonadal TR (NHTR) (&gt;8.0nmol/L) and time to full TR (FTR) (&gt;10.5nmol/L) were estimated from the date of first available testosterone at trial enrolment to the date of TR using the Kaplan-Meier method. The effect of interactions between duration of ADT and patients’ age on TR was evaluated. Results: There were 1439 men with non-castrate testosterone at baseline (&gt;1.7nmol/L) who met the inclusion criteria for analysis, of which 220, 765 and 454 men had 3-, 6-, and 18-months of ADT. There were 959 (67%) men who had FTR at last follow-up. For men who had 3-, 6-, and 18-months of ADT, the median time (range) to NHTR were 5.5 (1.6-76.3), 12.2 (0.8-53.6), and 30.1 (2.8-90.4) months respectively, while the median time (range) to FTR were 6.2 (1.8-75.7), 15.2 (0.8-86.0), and 36.0 (18.1-85.5) months respectively. In the subset of 1160 men who had normal testosterone at baseline (&gt;10.5nmol/L), 851 (69%) men had FTR, with a median time (range) to FTR of 5.5 (1.8-75.7), 12.7 (1.8-86.0), and 30.8 (18.1-84.1) months for men who had 3-, 6- and 18-months ADT, respectively. For any given duration of ADT, men aged above 65 years were less likely to have FTR compared to those aged under 65 years – HR=0.67 (95%CI=0.46-0.99), HR=0.80 (95%CI=0.67-0.96), HR=0.64 (95%CI=0.51-0.81) for men who had 3-, 6-, and 18-months ADT respectively. There was no evidence of interaction between the effect of ADT duration on time to FTR and age (interaction P=0.3 for entire cohort). Conclusions: This is the largest pooled analysis of prospectively collected serial testosterone data from randomized trials, indicating substantial delay in FTR in men receiving longer durations of ADT. Approximately one-third of the men did not achieve FTR, which may have life-long impact on quality of life.
Stereotactic reirradiation for local prostate cancer recurrence: Mono-institutional experience of 108 patients.
Authors: Manon Baty, Joel Castelli, Khemara Gnep, Nolwenn Delaby, Romain Mathieu, Renaud de Crevoisier
Journal: Journal of Clinical Oncology (2023)

365 Background: The aim of this study was to report the efficacy and toxicity of salvage stereotactic body radiation therapy (SBRT) for local prostate cancer recurrence after radiotherapy. Methods: We retrospectively reviewed a total of 108 medical records of patients treated with salvage SBRT for prostate cancer recurrence, between July 2015 and February 2021 in our institution. Patients who had initial radical prostatectomy were excluded. The median time interval between the two radiation treatments was 9 years (range, 3-20 years). All the patients had biochemical recurrence, with a PSA of 3.5 ng/mL (range, 1.8-43 ng/mL). Local recurrence was to be proven by biopsies, without distant lymph node or metastasis. The local recurrence was visible in 82% and 99% of patients on mpMRI and choline/PSMA PET/CT, respectively. The salvage treatment consisted in SBRT at a total dose of 36 Gy in six fractions delivered every other day, associated with androgen deprivation therapy in 44% of patients. We reported efficacy and toxicity (according to CTCAE v 4.03 classification) after salvage SBRT. Results: Median follow-up was 19.6 months (range, 2.3-67 months). Two year biochemical recurrence-free survival and lymph node/metastases free survival rates were 76% (95% CI: 66-87%) and 88% (95% CI: 80-96%), respectively. Regarding acute toxicity, rates of grade 2 and 3 GU toxicities were 27% and 2%, respectively. Rate of grade 2 GI toxicity was 2%, without grade ≥3. Regarding late toxicity, 2 year rates of grade 2 and 3 GU toxicities were 50% (95% CI: 44-56%) and 8% (95% CI: 2-14%), respectively. One patient experimented a grade 4 GU toxicity (bladder necrosis requiring a cystectomy) 8 months after SBRT. Two year rate of grade 2 GI toxicity was 2 (95% CI: 0-5%), without grade ≥3. Conclusions: The main toxicity of prostate salvage SBRT is GU. With a short follow-up, a subset of patients may be controlled by the salvage treatment.
The impact of F-18 PSMA PET imaging on clinical decision-making in prostate cancer across disease states.
Authors: Ali Arafa, Aditya Jain, Brad Humphrey, Jerry Froelich, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2023)

63 Background: Piflufolastat F-18 (18F-DCFPyL) PSMA PET imaging was recently approved by the FDA for initial staging, biochemical recurrence (BCR), and restaging of metastatic prostate cancer. Given that the PSMA PET is a next-generation novel imaging modality that carries a higher sensitivity for detecting metastatic disease compared with conventional imaging, we aimed to assess how its integration into clinical care may have impacted the management of patients. Methods: We identified 236 patients who underwent an 18F-DCFPyL PET scan at the University of Minnesota between August 2021 to June 2022. The median PSA at the time of imaging was 1.75 ng/ml (range, 0.02 - 3740 ng/ml). All PSMA PET scans were evaluated by an experienced nuclear medicine physician. Descriptive statistics were used to analyze its impact on the clinical care of 158 patients: 22 for initial staging, 110 with biochemical recurrence, and 26 patients with known metastatic disease. The remaining 78 patients had no information available to assess clinical utility. Results: Metastatic PSMA-avid lesions were detected in 152/236 (64.4%) patients. In patients undergoing initial staging of high-risk prostate cancer, 17/40 (42.5%) patients had metastatic lesions outside the prostate involving 10 regional and 5 non-regional lymph nodes, 1 visceral site, and 10 bone metastases. 17/40 (42.5%) of the scans were unremarkable. 6/40 (15%) had equivocal scan results. For the patients with available clinical information, 12/22 (54.5%) had a change in their treatment plan post-DCFPyL, while 10/22 (45.5%) had no change. In the biochemical recurrence cohort, 93/151 (61.6%) had positive lesions: 28 local recurrences, 47 regional and 22 non-regional lymph nodes, 5 visceral and 28 bone metastases. Equivocal and negative scans accounted for 13/151 (8.6%) and 45/151 (29.8%) cases, respectively. 44/110 (40%) of the patients with clinical information had a change in their treatment plan, while the plan did not change for 66/110 (60%) cases. In patients with known metastatic prostate cancer undergoing restaging, 42/45 (93.3%) had DCFPyL-positive lesions; 12 local recurrences, 20 regional and 16 non-regional, 9 visceral, and 29 bone metastases. Equivocal and negative scans accounted for 2/45 (4.4%) and 1/45 (2.2) of cases, respectively. Only 11/26 (42.3%) of those with clinical information had their tentative treatment plan adjusted post-DCFPyL. No change in the treatment plan was made in 15/26 (57.7%) cases. Conclusions: Integration of the F-18 PSMA PET imaging substantially impacted clinical decision-making, especially for initial staging of high-risk localized disease (treatment change in 55%) and for biochemical recurrence (treatment change in 40%). It remains to be seen if this would translate into superior survival outcomes.
Patient and physician preferences for adjuvant treatment of renal cell carcinoma: A discrete-choice experiment.
Authors: Shawna R Calhoun, Caroline Vass, Kelley Myers, Kentaro Imai, Cooper Bussberg, Rituparna Bhattacharya, Cathy Anne Pinto, Christine Poulos
Journal: Journal of Clinical Oncology (2023)

635 Background: Although a handful of studies have elicited treatment preferences in renal cell carcinoma (RCC), most focused on advanced disease. This study elicited United States patients’ and physicians’ preferences for adjuvant treatment characteristics. Methods: Patients with physician-confirmed RCC and (physician-defined) intermediate high or high risk of recurrence and physicians who treat such patients completed online surveys in Q1-Q2 2022 with a discrete-choice experiment. Hypothetical treatments were described by median disease-free survival (DFS); 5-year overall survival (OS) rate; mode and frequency of administration; need for concomitant daily pill; treatment duration; and the risks of severe diarrhea, fatigue, and dizziness. Preference weight estimates from random parameter logit analysis were used to calculate the conditional relative importance of attributes and risk tolerance measures. Results: 250 patients (50% post-nephrectomy) and 250 physicians (64% oncologists; 36% urologists) completed the survey. OS was the most important attribute to both patients and physicians, but DFS was also important (Table). OS had a greater influence on physicians’ choices than on patients’ choices. On average, OS was 3.2 and 2.5 times as important as DFS and 5.8-9.1 and 2.4-3 times more important than the evaluated risks for physicians and patients, respectively. Further, DFS was 1.8-2.9 times more important to physicians than the evaluated risks, while the importance of DFS and risks were nearly equivalent for patients. The need for concomitant oral medication was the least important attribute to patients and physicians. Both groups were willing to accept more than a 25-percentage-point increase in the risks of severe diarrhea, fatigue, and dizziness for improvements (from 45% to 60% or 85%) in OS. Conclusions: While both patients and physicians weighted OS improvements more than the other treatment attributes, including risks, physicians tended to place lower importance on changes in risk and administration than patients. Physicians and patients should discuss potential benefits and harms when considering adjuvant RCC therapies. [Table: see text]
Phase II study of axitinib prior to partial nephrectomy to preserve renal function: An interim analysis of the PADRES clinical trial.
Authors: Kevin Hakimi, Steven Campbell, Mimi Nguyen, Nityam Rathi, Luke Wang, Brian I. Rini, Moshe Chaim Ornstein, Rana R. McKay, Ithaar H Derweesh
Journal: Journal of Clinical Oncology (2023)

683 Background: In renal cell carcinoma (RCC), partial nephrectomy (PN) is indicated for patients with solitary kidney, chronic kidney disease, or bilateral tumors. A subset of these patients, however, may have large and complex renal masses not initially suitable for PN. Neoadjuvant Tyrosine Kinase Inhibitor therapy has shown promising results in cytoreducing renal tumors and may permit PN in circumstances not otherwise feasible. Methods: This was a single arm phase II clinical trial of neoadjuvant axitinib in patients with complex (RENAL nephrometry score 10-12 and cT1b-cT3M0) biopsy-proven clear cell RCC with strong indications for partial nephrectomy (PN), and in whom radical nephrectomy may result in dialysis dependence. Axitinib 5 mg was administered orally twice daily for 8 weeks prior to surgery. Primary outcome was reduction in longest tumor diameter; secondary outcomes included tumor response (RECIST), change in RENAL score, feasibility of PN, change in estimated glomerular filtration rate (DeGFR), and post-surgical complications. Results: 26 patients were enrolled. 19 (73.1%) patients had ≥ clinical T3a staged tumors. Post therapy, 17 (65.4%) patients had ≥T3a staged tumors. Axitinib resulted in reductions in tumor size (7.7 vs. 6.3 cm, p&lt;0.001) and RENAL score (11 vs. 10, p &lt;0.001); 9 (34.6%) had partial response, and 17 (65.4%) stable disease by RECIST criteria. PN was successfully performed in 19 (73.1%); 24 (96.8%) achieved negative margins. Six (23.1%) had Clavien III-IV post-surgical complications. Median percentage DeGFR was 14.7%; one (3.8%) patient who had a radical nephrectomy had long-term dialysis dependence. Conclusions: Neoadjuvant axitnib resulted in significant reductions in tumor size and complexity, enabling PN in a cohort of complex renal masses, and with acceptable safety and functional preservation. Clinical trial information: NCT03438708 . [Table: see text]
CaboCombo: A prospective international non-interventional study of first-line cabozantinib plus nivolumab for the treatment of patients with advanced renal cell carcinoma.
Authors: Philippe Barthelemy, Pascale Dutailly, Bryan Qvick, Valérie Perrot, Elena Verzoni
Journal: Journal of Clinical Oncology (2023)

TPS740 Background: The combination of cabozantinib plus nivolumab (Cabo + Nivo) was approved in Europe in 2021 for the first-line (1L) treatment of patients with advanced renal cell carcinoma (aRCC) based on evidence from the phase 3 CheckMate 9ER trial. In the CheckMate 9ER trial (N = 651), Cabo + Nivo improved overall survival (hazard ratio [HR] 0.70 [95% confidence interval: 0.55–0.90]; p = 0.0043) and progression-free survival (HR 0.56 [95% CI: 0.46–0.68]; p ≤ 0.0001) versus sunitinib. There is clinical interest in the effectiveness and tolerability of Cabo + Nivo as used in routine cancer care. Methods: CaboCombo is a prospective, international, real-world non-interventional study to evaluate the effectiveness and tolerability of 1L Cabo + Nivo in adults (aged ≥ 18 years) with aRCC with a clear-cell component. In total 311 patients will be enrolled across 70 centers in countries where 1L Cabo + Nivo has marketing authorization and reimbursement. The decision to prescribe Cabo + Nivo will be made prior to, and independently from, the decision to enroll patients. The primary endpoint is real-world landmark overall survival assessed 18 months after Cabo + Nivo initiation. Secondary endpoints include: real-world treatment patterns; median progression-free survival; objective response rate; duration of response; disease control rate; time to response; treatment-emergent adverse events, and changes in disease-related symptoms and pain during the treatment period (assessed by the Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index – Disease Related Symptoms questionnaire, and the Numerical Pain Rating Scale). Patients will be enrolled over 24 months and followed for up to 42 months. The nature and timing of study visits and assessments will be as per usual care at each participating center; no additional diagnostic or monitoring procedures will be conducted. Treatment will continue until disease progression, unacceptable toxicity or withdrawal of participant consent. Two interim analyses will be conducted, the first a description of baseline characteristics when at least 50% of participants have been recruited. No changes in study design or conduct will be made based on the results of these analyses. Clinical trial information: NCT05361434 .
Impact of cytoreductive nephrectomy (CRN) on overall survival (OS) in metastatic non–clear cell renal cancer (nccRCC).
Authors: Ariel Ann Nelson, Aniko Szabo, Deepak Kilari
Journal: Journal of Clinical Oncology (2023)

730 Background: Non-clear cell renal cell carcinoma (nccRCC) accounts for 25% of kidney cancer diagnoses and encompasses a diverse group of kidney tumors with distinct biology for which treatment in the metastatic setting is evolving. The role of CRN for nccRCC population in the current treatment landscape remains unclear. Methods: We retrospectively identified patients (pts) with nccRCC from The National Cancer Database (NCDB) participant user file (PUF) for Kidney and Renal Pelvis Tumors. Pts with de novo metastatic disease diagnosed between 2006 and 2017, received systemic treatment (trt) with immunotherapy (IO) or non-immunotherapy (NIO) and either underwent or could have undergone a CRN were selected. Demographic and disease characteristics were summarized using descriptive statistics. The cumulative incidence of CRN with death without CRN as a competing risk, was estimated using the Nelson-Aalen estimator. The association of each demographic and disease characteristic on the cumulative incidence of CRN was evaluated using univariate Fine-Gray regression. The effect of CRN on survival was visualized using a Simon-Makuch plot. P values were based on Mantel-Byar test. Cox regression with a time-dependent predictor was used to estimate the change in the hazard of death after CRN. Results: We identified 3644 pts, 72% male, mean age 61 ±13 years. Nearly 40% of pts (n=1453) had sarcomatoid histology, followed by 30% with papillary (n=1075). Most pts, 96% (n=3489) received NIO systemic trt and only 9% were treated with IO (n=319). Nearly half of the study population (45%) underwent CRN (n=1642). Of these, 95% received NIO trt (n=1564) and 9% received IO (n=152). Pts who underwent CRN were younger and less likely to have bone, brain or liver metastases. Minority pts were less likely to undergo CRN. Mean time from dx to surgery was 1.1 ±1.7 months. For all pts, mOS was 9 months (95% CI: 8.6-9.4). OS was improved for pts who underwent CRN vs those who did not (11.3 vs 7.5 months, p&lt;0.0001). In multivariate analysis, cytoreductive nephrectomy was associated with a reduction in the risk of death, HR 0.73 (95% CI: 0.68, 0.80, p&lt;.0001). Conclusions: For pts with de novo metastatic nccRCC, CRN is associated with improved outcomes. Further analysis regarding the effect of treatment regimens on survival outcomes is warranted and planned. Prospective randomized trials in the modern treatment era are needed to further assess the timing and impact of CRN on outcomes in pts with metastatic nccRCC. [Table: see text]
Evaluating the clinical utility of circulating tumor cells (CTC) profiling to predict selection of preferred therapeutic regimens in newly diagnosed or pretreated refractory renal cell carcinomas (RCC).
Authors: Ulka N. Vaishampayan, Jeremy MG Taylor, Ajjai Shivaram Alva, Neha Shah, Anuja Mhalsekar, Rahul Ashok Gosavi, Sachin Apurwa, Darshana Patil
Journal: Journal of Clinical Oncology (2023)

717 Background: There is an unmet need for biomarkers enabling therapeutic selection and prediction of clinical outcomes in kidney cancer . We evaluated the feasibility and utility of profiling of circulating tumor cells (CTCs) via multiplexed fluorescence immunocytochemistry (ICC) to identify liquid biopsy biomarkers linked to treatment response (or resistance) in advanced RCC patients. In addition, transcriptome analysis for 20802 genes from exosomal RNA is planned to evaluate novel prognostic and predictive signatures. Methods: Patients with either untreated or pretreated advanced RCC were eligible prior to starting a new systemic therapy regimen. IRB approved written informed consent was obtained. Serial blood samples were collected at baseline, and at 3, 6, 12 and 24 months. Primary endpoint of the study was to detect the proportion of patients with RCC in whom CTCs can be detected and profiled. Secondary endpoints are to correlate the profiling and changes in CTC with response and clinical outcomes. The study will meet its primary endpoint if the assay provides adequate detection and profiling for at least 12 patients. With an overall sample size of 50 the width of a 95% confidence interval for the rate of providing a therapeutic intervention is guaranteed to be less than 26%. Results: 44 evaluable patients have been enrolled; 11 females, 33 males. Median age was 64 years (range 40-85 years). 38 white patients, 2 black patients and 4 of other ethnicity have been enrolled.16 patients were untreated, 22 were pretreated and 6 were undergoing adjuvant therapy post nephrectomy. 37 patients had clear cell histology, 4 non clear cell and 3 unclassified histology. 42 of the 44 (95.5%) patients had detectable CTCs in the baseline sample. 21 on treatment samples have been collected to date, with detectable CTCs in all except one sample. 53 of 65 samples (81.5%) demonstrated detection of at least one biomarker by ICC. VEGFA expression was the most commonly detected biomarker on ICC (detected in 28 of 63 samples). Conclusions: The primary endpoint was met, and feasibility of the test was demonstrated with 95% of the baseline samples showing CTC detection and 81.5% showing biomarker expression. This blood-based, non-invasive liquid biopsy demonstrated high sensitivity for detection of cancer cells, and presents a potential opportunity for biomarker profiling to predict therapeutic efficacy of conventional RCC therapeutic agents. Correlation of longitudinal CTC with clinical outcomes will be reported. Transcriptome analysis is under evaluation for novel prognostic and predictive signatures and will be reported.
Androgen receptor (AR) mutations in men with metastatic castration-resistant prostate cancer (mCRPC): Incidence and natural history.
Authors: Alice Bernard-Tessier, Guillaume Mulier, Paula Nay, Capucine Baldini, Laurence Albiges, Emeline Colomba, Ronan Flippot, Pernelle Lavaud, Natacha Naoun, Anna Patrikidou, Yohann Loriot, Christophe Massard, Stéphanie Foulon, Karim Fizazi
Journal: Journal of Clinical Oncology (2023)

221 Background: AR ligand binding domain (LBD) activating somatic point mutation is a known mechanism of resistance to androgen-receptor signaling inhibitor (ARSI) treatment in mCRPC, leading to a persistent addiction to steroid hormones. Two early phase trials investigating CYP11A1 inhibitors - CYPIDES (ODM208, NCT03436485) and STESIDES (ODM209, NCT03878823) - recruited mCRPC patients with and without pre-specified AR LBD mutation. In CYPIDES Part 1, AR LBD mutations (ARm) strongly predicted for PSA decline with ODM-208 (Fizazi, ASCO GU 2021). Here, we evaluated clinical and genomic data associated with ARm in patients with mCRPC. Methods: We reviewed clinical and molecular data from patients with mCRPC who progressed after ≥1 ARSI and ≥1 line of taxane-based chemotherapy or were ineligible to chemotherapy, pre-screened in CYPIDES and STESIDES trials at our center. Circulating tumor DNA (ctDNA) was tested for AR LBD mutation (Guardant360 CDx and Sysmex OncoBEAM) and for genomic analysis (FoundationOne Liquid CDx, STING trial, NCT04932525) to screen for actionable targets. Results: From March 2020 to January 2022, 272 men were screened. Median age was 62y. Overall, 212 (78%), 202 (74%), and 240 (88%) patients had received previous abiraterone, enzalutamide, and docetaxel respectively. Median PSA at screening was 59 ng/mL (IQR 11; 246). ARm was found in 69 patients (25%). The most frequent mutations were L702H (15%), T878A (12%), H875Y (7%), V716M (2%), F877L (2%), W742C (1%), globally consistent with previous reports. Associations of ARm with relevant baseline characteristics of patients are summarized. Duration of enzalutamide exposure was correlated with the number of AR mutations per patient (p = 0.006) whereas no correlation was found for abiraterone exposure duration (p=0.71). In 173 (64%) patients with available genomic testing, no alterations were found to be mutually exclusive with ARm, including in DNA repair alteration. Conclusions: AR LBD mutations were detected in ctDNA in 25% of men with advanced mCRPC treated with at least one ARSI. Their incidence was associated with a longer duration of treatment with enzalutamide and a longer time from CRPC and prostate cancer diagnosis. [Table: see text]